Cost-effectiveness analysis of transcatheter aortic valve implantation in aortic stenosis patients at low- and intermediate-surgical risk in Japan.

OBJECTIVE: To analyze the cost-effectiveness of transcatheter aortic valve implantation (TAVI) using the SAPIEN 3 (Edwards Lifesciences, Irvine, CA) compared to surgical aortic valve replacement (SAVR) in low- and intermediate-risk patients from a Japanese public healthcare payer perspective. METHODS: A Markov model cost-effectiveness analysis was developed. Clinical and utility data were extracted from a systematic literature review. Cost inputs were obtained from analysis of the Medical Data Vision claims database and supplemented with a targeted literature search. The robustness of the results was assessed using sensitivity analyses. Scenario analyses were performed to determine the impact of lower mean age (77.5 years) and the effect of two different long-term mortality hazard ratios (TAVI versus SAVR: 0.9-1.09) on both risk-level populations. This analysis was conducted according to the guidelines for cost-effectiveness evaluation in Japan from Core 2 Health. RESULTS: In intermediate-risk patients, TAVI was a dominant procedure (TAVI had lower cost and higher effectiveness). In low-risk patients, the incremental cost effectiveness ratio (ICER) for TAVI was ¥750,417/quality-adjusted-life-years (QALY), which was below the cost-effectiveness threshold of ¥5 million/QALY. The ICER for TAVI was robust to all tested sensitivity and scenario analyses. CONCLUSIONS: TAVI was dominant and cost-effective compared to SAVR in intermediate- and low-risk patients, respectively. These results suggest that TAVI can provide meaningful value to Japanese patients relative to SAVR, at a reasonable incremental cost for patients at low surgical risk and potentially resulting in cost-savings in patients at intermediate surgical risk.

Aortic Stenosis (AS) is the most common valvular heart disease in Japan, and, if left untreated, severe symptomatic AS (sSAS) is associated with a dramatic increase in mortality and morbidity. Transcatheter Aortic Valve Implantation (TAVI) is a minimally invasive treatment option for replacing the aortic valve in patients with sSAS and has been associated with similar or better outcomes compared to Surgical Aortic Valve Replacement (SAVR), which involves open-heart surgical replacement of the aortic valve. The objective of this study was to compare the costs and health outcomes associated with TAVI compared to SAVR in Japanese patients deemed low- or intermediate-risk for surgery. Despite the expanding use of TAVI in Japan, a cost-effectiveness analysis (CEA) does not exist that evaluates the economics of TAVI with the current generation SAPIEN 3 implant in patients with low- and intermediate-risk from a public perspective. Our study suggests that TAVI represents strong value for money among low- and intermediate-risk patients in Japan: compared to SAVR, TAVI is associated with better clinical outcomes and quality of life for patients, at a reasonable additional cost for low-risk patients and at a lower cost for intermediate-risk patients.

Patient preferences for heart valve disease intervention.

BACKGROUND: This study aimed to determine how patients trade-off the benefits and risks of two different types of procedures used to treat heart valve disease (HVD). It also aimed to determine patients' preferences for HVD treatments (predicted uptake) and the relative importance of each treatment attribute. METHODS: A discrete choice experiment (DCE) was conducted in Australia and Japan with patients who required a heart valve procedure. Patients were stratified into three categories: no prior procedure experience, minimally invasive procedure experience and invasive procedure experience. DCE attributes included risk of mortality; risk of stroke; needing dialysis; needing a new pacemaker; valve durability; independence 1 month after surgery; and out-of-pocket expenses. Participants chose between two hypothetical labelled approaches to therapy ('invasive procedure' and 'minimally invasive procedure'), with a separate opt-out included. A mixed multinomial logit model was used to analyse preferences. RESULTS: The DCE was completed by 143 Australian and 206 Japanese patients. Both populations demonstrated an overall preference for the minimally invasive procedure over the invasive procedure. All attributes tested significantly predicted choice and were important to patient decision-making. However, patients' choices were most influenced by the durability of the valve and the likelihood of independence postprocedure, irrespective of their prior procedure experience. Differences in preference were observed between Australian and Japanese patients; valve durability was the most important attribute among Australian patients, while Japanese patients emphasised regaining independence postsurgery. Risk of mortality was less important relative to other key attributes in Japan; however, it remained significant to the model. CONCLUSIONS: HVD patients prefer a minimally invasive procedure over an invasive procedure, irrespective of prior treatment experience. Key attributes contributing to treatment preferences are valve durability and faster recovery. These results can be used to help inform healthcare decision-makers about what features of heart valve procedures patients value most. PATIENT AND PUBLIC CONTRIBUTION: People with lived experience of HVD were included in multiple stages of the design phase of this research. First, patients and doctors were consulted by taking part in qualitative interviews. The qualitative interviews helped inform which treatment attributes to include in the DCE based on what was important to those with lived experience and those who help make treatment decisions on behalf of patients. Qualitative interview participants also assisted with the framing of questions in the online survey to ensure the terminology was patient-friendly and relevant to those with lived experience. Following qualitative interviews, the DCE attribute list was agreed on in expert consultation with a steering committee, which included patient representatives and treating physicians (interventional cardiologists, cardiothoracic surgeons). The survey was also pilot tested with a small sample of patients and minor adjustments were made to the wording to ensure it was appropriate and meaningful to those with lived experience of HVD.

In-Hospital Outcomes of Heart Failure Patients with Valvular Heart Disease: Insights from Real-World Claims Data.

Purpose: Heart failure (HF) is a serious public health burden that is rapidly increasing in the aging population. Valvular heart disease (VHD) is a known etiology of heart failure (HF); however, the impact of VHD on outcomes of patients with HF has not been well-studied in Japan. This study aimed to determine the rates of VHD in Japanese patients admitted for HF and explore associations of VHD with in-hospital outcomes through a claim-based analysis. Patients and methods: We analyzed claims data from 86,763 HF hospitalizations (January 2017 through December 2019) from the Medical Data Vision database. Common etiologies of HF were examined, then hospitalizations were categorized into those with VHD and those without. Covariate-adjusted models were used to explore the association of VHD with in-hospital mortality, length of stay, and medical cost. Results: Of 86,763 hospitalizations for HF, 13,183 had VHD and 73,580 did not. VHD was the second most frequent etiology of HF (15.2%). The most frequent type of VHD was mitral regurgitation (36.4% of all hospitalizations with VHD), followed by aortic stenosis (33.7%) and aortic regurgitation (16.4%). There was no significant difference in in-hospital mortality between hospitalizations with VHD vs those without (9.0% vs 8.9%; odds ratio [95% CI]: 1.01 [0.95-1.08]; p=0.723). Hospitalizations with VHD were associated with significantly longer length of stay (26.1 vs 24.8 days; incident rate ratio [95% CI]: 1.05 [1.03-1.07]; p<0.001) and higher medical costs (1536 vs 1195 thousand yen; rate ratio [95% CI]: 1.29 [1.25-1.32]; p<0.001). Conclusion: VHD was a frequent etiology of HF that was associated with significant medical resource use. Future studies are needed to investigate whether timely VHD treatment could reduce HF progression and its associated healthcare resource utilization.

Enhancement of Acinetobacter baumannii biofilm growth by cephem antibiotics via enrichment of protein and extracellular DNA in the biofilm matrices.

AIMS: The aims were to determine the effects of subinhibitory concentrations of eight cephem and carbapenem antibiotics on the biofilm formation of Acinetobacter baumannii cells and examine their effects on pre-established biofilms. METHODS AND RESULTS: Effects of antibiotics on biofilm formation were assayed using microtitre plates with polystyrene peg-lids. Cefmetazole, ceftriaxone, ceftazidime and cefpirome increased the biomass of pre-established biofilms on pegs in the range of their sub-minimum inhibitory concentrations (MICs), whereas none increased biofilm formation by planktonic cells. Carbapenems had a negative effect. The constituents of antibiotic-induced biofilms were analysed. Ceftriaxone or ceftazidime treatment markedly increased the matrix constituent amounts in the biofilms (carbohydrate, 2.7-fold; protein, 8.9-12.7-fold; lipid, 3.3-3.6-fold; DNA, 9.1-12.2-fold; outer membrane vesicles, 2.7-3.8-fold and viable cells, 6.8-10.1-fold). The antibiotic-enhanced biofilms had increased outer membrane protein A and were resistant to the anti-biofilm effect of azithromycin. CONCLUSIONS: Some cephems increased the biomass of pre-established biofilms in the ranges of their sub-MICs. The antibiotic-enhanced biofilms possessed more virulent characteristics than normal biofilms. SIGNIFICANCE AND IMPACT OF THE STUDY: Incomplete administration of certain cephems following biofilm-related Ac. baumannii infections could adversely cause exacerbated and chronic clinical results.

Direct anti-biofilm effects of macrolides on Acinetobacter baumannii: comprehensive and comparative demonstration by a simple assay using microtiter plate combined with peg-lid.

Recently, opportunistic nosocomial infections caused by Acinetobacter baumannii have become increasingly prevalent worldwide. The pathogen often establishes biofilms that adhere to medical devices, causing chronic infections refractory to antimicrobial therapy. Clinical reports have indicated that some macrolide antibiotics are effective against chronic biofilm-related infections. In this study, we examined the direct anti-biofilm effects of seven macrolides (azithromycin, clarithromycin, erythromycin, josamycin, spiramycin, fidaxomicin, and ivermectin) on A. baumannii using a simple and newly established in vitro assay system for the swift and serial spectrophotometric determinations of two biofilm-amount indexes of viability and biomass. These macrolides were found to possess direct anti-biofilm effects exerting specific anti-biofilm effects not exclusively depending on their bacteriostatic/bactericidal effects. The anti-biofilm effect of azithromycin was found to be the strongest, while those of fidaxomicin and ivermectin were weak and limited. These results provide insights into possible adjunctive chemotherapy with macrolides for A. baumannii infection. Common five macrolides also interfered with the Agrobacterium tumefaciens NTL(pCF218) (pCF372) bioassay system of N-acyl homoserine lactones, providing insights into sample preparation for the bioassay, and putatively suggesting the actions of macrolides as remote signals in bacterial quorum sensing systems.

Cost-Effectiveness Analysis of Vedolizumab Compared with Other Biologics in Anti-TNF-Naïve Patients with Moderate-to-Severe Ulcerative Colitis in Japan.

BACKGROUND: Vedolizumab (VDZ) was approved by the Japanese Ministry of Health, Labor and Welfare in 2018 for the treatment of patients with moderate-to-severe active ulcerative colitis (UC). The comparative cost-effectiveness of VDZ compared with other biologics is unknown in Japan. This information could be useful for decision makers at the time of repricing biologics for the treatment of patients with moderate-to-severe UC. OBJECTIVE: The aim was to assess the cost-effectiveness of VDZ versus other branded biologics for the treatment of patients with moderate-to-severe UC who were anti-tumor necrosis factor (TNF)-naïve, from the Japanese public healthcare payer perspective. METHODS: A hybrid decision tree/Markov model was developed to predict the number of patients who achieved response and remission at the end of the induction phase and sustained it during the maintenance phase, translating this into quality-adjusted life-years (QALYs) and costs. Treatment-related adverse events, discontinuation and surgery, and their impact on QALYs and costs were also modeled. A systematic literature review and network meta-analysis were conducted to estimate the comparative efficacy of each treatment versus placebo. Rates of adverse events, surgery, surgery complications, and utilities were from the literature. Costs (2018 Japanese yen) were obtained from the Japanese National Health Insurance drug price list and medical fee table and local claims databases. Clinical and economic outcomes were projected over a lifetime and discounted at 2% annually. RESULTS: Over a lifetime, VDZ yielded greater QALYs and cost savings compared with golimumab and was cost-effective compared with adalimumab and infliximab (incremental cost-effectiveness ratios ¥4,821,940 and ¥4,687,692, respectively). Deterministic and probabilistic analyses supported the robustness of the findings in the base-case analysis, indicating that VDZ was either dominant or cost-effective in most scenarios and replications. The main limitations of this analysis include excluding tofacitinib and infliximab biosimilar as comparators, health-state utility estimates were obtained from population studies in the United Kingdom, and the impact of subsequent (i.e., second-line) biologic treatment was not evaluated. CONCLUSION: Our analysis suggests that VDZ is dominant or cost-effective compared with other branded biologics for the treatment of anti-TNF-naïve patients with moderate-to-severe UC in Japan.

Health-related quality of life outcomes and economic burden of inflammatory bowel disease in Japan.

PURPOSE: Previous Japanese studies have not compared health-related quality of life (HRQoL), work productivity and activity impairment, health care resource utilization (HRU), and costs in inflammatory bowel disease (IBD) patients with non-IBD controls, leading to insufficient evidence regarding IBD's true burden. The aim of this study was to examine the impact of IBD on patient-reported outcomes and costs among Japanese adults (≥18 years). PATIENTS AND METHODS: This retrospective cross-sectional study used data from the 2012-2014 Japan National Health and Wellness Survey (N=83,505). HRQoL (SF-36v2), work productivity and activity impairment (work productivity and activity impairment-General Health Questionnaire), HRU, and annual costs were compared between respondents with IBD (n=441) and non-IBD controls (n=82,944), and within IBD subtypes (Crohn's disease [CD] and ulcerative colitis [UC]) using chi-square and ANOVA tests. RESULTS: Mental Component Summary (MCS), Physical Component Summary (PCS), and health state utility (Short-Form-6 Dimensions [SF-6D]) scores were significantly lower in IBD respondents than in controls (differences of 2.2 points, 2.6 points, and 0.041 points, respectively; all P<0.001). However, only differences in SF-6D scores reached the minimally important difference threshold. Furthermore, IBD-diagnosed respondents reported greater absenteeism, presenteeism, overall work productivity loss and activity impairment, and HRU than controls (all P<0.001). Consequently, direct and indirect costs were 3-fold and 1.5-fold higher in IBD-diagnosed respondents than in controls (both, P<0.001). Additionally, CD-diagnosed respondents had lower MCS, PCS, and SF-6D scores (all P<0.01) and higher direct costs (P<0.001) than UC-diagnosed respondents. CONCLUSION: IBD and its subtype CD were associated with lower HRQoL, greater impairment to work and non-work activities, HRU, and costs among Japanese adults. This reinforces the general consensus that IBD patients, specifically those diagnosed with CD, require support from their family and society to combat the disease.

Health-related quality of life outcomes, economic burden, and associated costs among diagnosed and undiagnosed depression patients in Japan.

PURPOSE: Depression is associated with substantial health and economic burden. This study examined the impact of diagnosed and undiagnosed depression on health-related outcomes and costs among Japanese adults. METHODS: A retrospective, observational study was conducted using 2012-2014 Japan National Health and Wellness Survey (N=83,504) data. Differences between respondents diagnosed with depression (n=2,843) and undiagnosed with depression (weighted n=2,717) and controls without depression (weighted n=2,801) in health-related quality of life, impairment to work productivity and daily activities (Work Productivity and Activity Impairment Questionnaire), health care resource utilization, and annual costs were evaluated. Propensity score weighting and weighted generalized linear models were used to compare groups on the outcome variables, after adjusting for covariates. RESULTS: Overall, respondents with undiagnosed depression had significantly better outcomes than those diagnosed with depression, but significantly worse outcomes than controls (for all, P<0.001). The mean Mental Component Summary scores were lower in the diagnosed group when compared with undiagnosed respondents and controls (33.2 vs 34.5 vs 48.6). Similar findings were obtained for mean Physical Component Summary (49.2 vs 49.5 vs 52.8) and health state utility scores (0.61 vs 0.62 vs 0.76). Additionally, the diagnosed group reported greater absenteeism (13.1 vs 6.6 vs 2.5%), presenteeism (41.4 vs 38.1 vs 18.8%), overall work productivity impairment (47.2 vs 41.1 vs 20.2%), and activity impairment (48.4 vs 43.3 vs 21.1%) than the undiagnosed and control groups, respectively. Consistently, patients with diagnosed depression had higher annual per patient direct (1.6-fold) and indirect costs (1.1-fold) than those in the undiagnosed depression group. CONCLUSION: Diagnosed depression was associated with lower health-related quality of life and greater impairment in work productivity and daily activities, higher health care resource utilization, and higher costs, compared with undiagnosed respondents and controls. These study findings suggest a need for greater awareness of depression symptoms among Japanese adults, which is needed to facilitate proper diagnosis and treatment.

Health-related outcomes, health care resource utilization, and costs of multiple sclerosis in Japan compared with US and five EU countries.

PURPOSE: Multiple sclerosis (MS) imposes a huge burden on patients. This study examined the relationship between MS and health-related and economic burden in Japan; secondarily, health status was compared across patients with MS in Japan, US, and five European Union (5EU) countries (France, Germany, Italy, Spain, and UK). METHODS: A retrospective cross-sectional study was conducted using self-reported data from 2009 to 2014 Japan National Health and Wellness Survey (n=145,759). Health status, work productivity loss, activity impairment, health care resource utilization, and annual costs associated with MS (n=85) were compared with controls without MS (n=145,674). Propensity score matching and multivariable linear regressions determined the effect of MS after controlling for confounders. Health status in Japan was also compared with that of 5EU (n=62) and US (n=67) patients with MS. RESULTS: Patients with MS in Japan reported significantly worse health status via mental component summary score (MCS; 40.1 vs 45.8) and physical component summary score (PCS; 41.4 vs 51.2) and health state utility scores (0.63 vs 0.74; all P<0.001). They also reported more absenteeism (12.0% vs 3.7%), presenteeism (33.8% vs 19.8%), overall work impairment (40.9% vs 21.6%), and activity impairment (43.6% vs 24.0%), with higher indirect costs (¥2,040,672/US $20,102 vs ¥1,076,306/US$10,603) than controls (all P<0.001). Patients with MS reported higher resource use, including provider visits (8.0 vs 4.7), emergency room visits (0.03 vs 0.1), and hospitalizations (2.7 vs 0.69) in the past 6 months, with higher direct costs (¥3,670,906/US$36,162 vs ¥986,099/US$9,714) than controls (all P<0.001). Finally, Japanese patients with MS reported lower MCSs and higher PCSs than their US and 5EU counterparts. CONCLUSION: MS in Japan is associated with poor health status and high work productivity loss, resource use, and costs, underscoring the need for improved treatment, especially vis-à-vis mental health, when comparing Japanese patients with their 5EU and US counterparts.

Health-related quality-of-life, work productivity, and economic burden among patients with Parkinson's disease in Japan.

AIMS: This study aimed to characterize the burden of Parkinson's disease (PD) by examining health-related quality-of-life (HRQoL), impairments to work productivity and daily activities, healthcare resource use, and associated costs among Japanese patients with PD. MATERIALS AND METHODS: This retrospective cross-sectional study used data from the 2009-2014 Japan National Health and Wellness Survey (NHWS) (n = 144,692). HRQoL (Short Form 36-Item Health Survey version 2), impairments to work productivity and daily activities (Work Productivity and Activity Impairment Questionnaire), healthcare resource utilization, and annual costs were compared between respondents with PD (n = 133) and controls without PD (n = 144,559). The effect of PD on outcomes was estimated using propensity score weighting and multivariable regression models. RESULTS: HRQoL was lower in patients with PD compared to the control group, with reduced physical (41.3 vs 51.3) and mental (35.7 vs 45.4) component summary scores and health state utility scores (0.62 vs 0.77; p < .001 for all). Patients with PD also reported higher levels of absenteeism (19.3% vs 3.3%), presenteeism (45.2% vs 18.5%), overall work impairment (52.8% vs 20.3%), and activity impairment (49.6% vs 20.8%) than controls without PD (p < .001 for all). In addition, patients with PD had higher healthcare resource utilization, direct (¥3,856,921/$37,994 vs ¥715,289/$7,046), and indirect (¥2,573,938/$25,356 vs ¥902,534/$8,891) costs compared with controls without PD (p < .001 for both). LIMITATIONS: Data were cross-sectional and did not allow for causal inferences. Although the NHWS demographically represents the Japanese adult population, it is unclear whether it adequately represents the adult population with PD in Japan. CONCLUSIONS: PD was associated with poorer HRQoL, greater work productivity loss, and higher direct and indirect costs. The findings suggest that an unmet need exists among patients with PD in Japan. Improving PD treatment and management could benefit both patients and society.

Characterizations of the submerged fermentation of Aspergillus oryzae using a Fullzone impeller in a stirred tank bioreactor.

A Fullzone (FZ) impeller was used in the first study of the characteristics involved in the fermentation of Aspergillus oryzae. Both the experimental and simulation results of this study revealed novel findings into the positive relationship between the global-axial mixing patterns of a FZ impeller and fermentation efficiency. The mixing results when using the FZ impeller compared with a double Rushton turbine (DRT) impeller indicated that the culture mixed by the FZ resulted in a more homogeneous medium with higher values for oxygen mass transfer, cell growth rate, and alpha amylase activity. The simulation of fluid flow was done in a laminar regime using a two-fluid model. According to the simulation results, the maximum shear stress when using the DRT was higher than that with the FZ at the same power input (Pin). A high degree of local shear stress and the shear rate near the turbine blade of the DRT resulted in cell damage and a reduction in the enzyme activity, biomass, pellet diameter, and dissolved oxygen concentration. Calculations using the Brown equation showed that the maximum and average shear rates during mixing with the FZ impeller were lower than that when using the DRT. Therefore, the use of an FZ impeller, particularly at low Pin, enhanced the cultivation of A. oryzae.

Cost-effectiveness of a pentavalent rotavirus vaccine in Japan.

OBJECTIVE: To evaluate the impact of universal vaccination with a pentavalent rotavirus vaccine (RV5) on the healthcare burden and costs associated with rotavirus gastroenteritis (RGE) in Japan. METHODS: The model included a hypothetical cohort of 1,091,156 children followed for their first 5 years of life. In the absence of universal vaccination, there were 19 deaths, 78,000 hospitalizations, and 678,000 outpatient visits due to RGE. The efficacy of RV5 is based on international clinical trial data, which was similar to the efficacy observed in clinical trials conducted in Japan. The primary outcome measure is the cost per quality-adjusted-life-year (QALY) gained. In the base case, the QALY loss per 1000 RGE episodes included 2.2 for children and 1.8 per parent. RESULTS: Universal vaccination is projected to reduce hospitalizations by 92%, outpatient visits by 74%, and work-loss days by 73%. For the base case analysis, the total vaccination cost was ¥26 billion. The estimated reduction in medical costs was ¥16 billion. Of 2500 QALYs gained with the vaccination program, approximately half are directly attributed to the child. In the base case analysis, the incremental cost-effectiveness ratio (ICER) for vaccination vs. no vaccination is ¥4 million and ¥2 million per quality-adjusted life year (QALY) gained from the healthcare payer and societal perspectives, respectively. The ICERs are ¥8 million and ¥4 million if parental disutilities are excluded. KEY LIMITATION: The QALY decrements for children and parents were evaluated using different instruments, and the QALY decrements do not vary based on episode severity. Given the interdependence between children and their parents, excluding parental disutilities may under-estimate the impact of RGE. CONCLUSION: Universal vaccination with RV5 in Japan is projected to have a substantial public health impact and may be cost-effective from both the payer and societal perspectives if parental disutilities are included in the cost-effectiveness ratios.

The Cost-Effectiveness Analysis of a Quadrivalent Human Papillomavirus Vaccine (6/11/16/18) for Females in Japan.

OBJECTIVE: We assessed the epidemiological and economic impact of a quadrivalent human papillomavirus (HPV) (6/11/16/18) vaccine for females in preventing cervical cancer, cervical intraepithelial neoplasia grades 2 and 3 (CIN 2/3), cervical intraepithelial neoplasia grade 1 (CIN 1), and genital warts in Japan by using a transmission dynamic model. METHODS: A published mathematical model of the transmission dynamics of HPV infection and disease was adapted for Japan. Model inputs were used from Japan or the Asia/Pacific region when available; otherwise, the default values in the original model were used. The transmission dynamic model was used to assess the epidemiological and economic impact of a quadrivalent HPV (6/11/16/18) vaccine for females in preventing cervical cancer, CIN 2/3, CIN 1, and genital warts in Japan.Maintaining current cervical cancer screening practices, we evaluated two strategies: routine vaccination of females by age 12 years (S1), and S1 combined with a temporary (5 years) female catch-up program for age 12 to 24 years (S2). The vaccine coverage rate was 80% for the routine and 50% for the catch-up vaccination programs. RESULTS: Compared with no vaccination, both vaccination strategies significantly reduced the incidence of HPV 6/11/16/18-related disease. The most effective strategy was S2. By using this strategy over 100 years in the Japanese population, the estimated cumulative percentage reduction in incident HPV 6/11/16/18-related genital warts-female, genital warts-male, cervical CIN 1, CIN 2/3, and cervical cancer cases was 90% (2,113,723 cases), 86% (2,082,637 cases), 72% (263,406 cases), 71% (1,328,366 cases), and 58% (323,145 cases), respectively. The cost-effectiveness ratios were JPY 1,244,000, and JPY 1,205,800 per quality-adjusted life-year gained for S1 and S2 compared with no vaccination, respectively, over a time horizon of 100 years. CONCLUSION: We conclude that a quadrivalent HPV vaccination program for females can reduce the incidence of cervical cancer, CIN, and genital warts in Japan at a cost-per-quality-adjusted life-year ratio within the range defined as cost-effective.

Eye-concentrated distribution of dexamethasone carried by sugar-chain modified liposome in experimental autoimmune uveoretinitis mice.

Corticosteroid is generally accepted as a standard therapeutic agent for active inflammatory (and) autoimmune eye diseases. In an attempt to develop a system to deliver corticosteroid most efficiently to the target eye, a sialyl-Lewis X (sLe(x))-conjugated liposome was adopted as a candidate for a carrier of dexamethasone (Dexa) and tissue distribution of intravenous Dexa with the modified liposome as well as Dexa alone as control was studied in normal and experimental autoimmune uveoretinitis (EAU) mice. Intravenous Dexa (1 mg) was widely distributed in all the tissues (eye, brain, heart, lung, liver, kidney, spleen and intestine) examined in similar manner in both mice and Dexa concentration was lowest in the eye except the brain. The tissue concentrations of Dexa in EAU group were all significantly lower than those in the corresponding tissues in normal group. Intravenous Dexa (2 microg) in the modified liposome was almost concentrated to the eye in EAU mice, reaching 13.84 ng/mg tissue in contrast to 2.34 ng/mg tissue in Dexa (1 mg) alone administered EAU mice. In normal mice, Dexa was undetectable in any tissues examined and thus the effect of the modified liposome was not observed. The result supported the potentiality of sLe(x)-conjugated liposome for target-delivering of corticosteroid to inflamed eye.

Successful use of icodextrin in elderly patients on continuous ambulatory peritoneal dialysis.

In peritoneal dialysis (PD), a 7.5% polyglucose-containing dialysis solution (icodextrin) provides prolonged ultrafiltration as compared with glucose-based dialysis solutions. In the present study, we attempted to clarify the safety and effectiveness of icodextrin in elderly patients on continuous ambulatory peritoneal dialysis (CAPD). Clinical data and outcomes of 16 patients aged 65 or older were monitored for 12 weeks before and during icodextrin treatment. The group included 13 men and 3 women with a mean age of 69 +/- 5 years (range: 66-78 years). The underlying kidney disease was chronic nephritis in 7 patients, diabetes mellitus in 8 patients, and nephrosclerosis in I patient. From the beginning of peritoneal dialysis, 1 patients had been treated with icodextrin; the other 10 were changed to icodextrin from glucose dialysis solution. At the end of study, body weight had increased to 63.8 +/- 9.3 kg from 61.6 +/- 9.3 kg, accompanied by an increase in ultrafiltration to 480 +/- 207 mL daily from 369 +/- 436 mL daily. No significant change in urine volume occurred. Despite the increase in body weight, cardiothoracic rate decreased to 51.1% +/- 3.4% from 52.3% +/- 4.9%. All patients reported an improvement of edema and appetite. Edema scores were significantly decreased to 0.85 +/- 0.90 from 1.63 +/- 0.96 (p < 0.03). No adverse side effects were associated with the use of icodextrin. From the foregoing data, we concluded that, as compared with conventional glucose solution, icodextrin has beneficial effects on ultrafiltration volume and clinical symptoms in elderly patients on CAPD.

Expression of galanin receptor-1 (GALR1) in the rat trigeminal ganglia and molar teeth.

The expression of galanin receptor-1 (GALR1) was investigated in the rat trigeminal ganglion by using immunocytochemistry and in situ hybridization. In addition, the regional distribution of GALR1-immunoreactive pulpal nerves and their ultrastructure were examined in the molar teeth. In the trigeminal ganglion, the immunoreactivity for GALR1 was recognizable in about 30% of the total number of neurons. Most of the cell bodies were small to medium in size. Analysis of serially cut sections alternately stained with GALR1 and galanin antisera demonstrated that some GALR1-positive cells displayed immunoreactivity for galanin. In situ hybridization analysis, expression of GALR1 mRNA was detected in trigeminal ganglion cells. The cell size distribution was similar to that of GALR1-immunoreactive cells. In the dental pulp, a small number of nerve fibers displayed immunoreactivity for GALR1. The labeled fibers formed terminal arbors in the coronal pulp around and within the odontoblast cell layer, but never penetrated into the predentin and dentin. Ultrastructurally, GALR1 immunoreactivity in the dental pulp was confined to the axoplasm of unmyelinated nerve fibers. The present study provided new evidence that unmyelinated primary afferents innervating dental pulp possessed galanin receptor, and suggests the existence of nociceptive primary afferents functioning as autocrine cells.